2-amino-N,N-bis[2'-(tert-butyldimethylsilyloxy)ethyl]aniline | 528836-35-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-amino-N,N-bis[2'-(tert-butyldimethylsilyloxy)ethyl]aniline
• 英文别名: 2-amino-bis[2'-(tert-butyldimethylsilyloxy)ethyl]-aniline；2-N,2-N-bis[2-[tert-butyl(dimethyl)silyl]oxyethyl]benzene-1,2-diamine
• CAS: 528836-35-3
• 化学式: C₂₂H₄₄N₂O₂Si₂
• 分子量: 424.775
• InChiKey: XZJIBVDEJKMXGL-UHFFFAOYSA-N

物化性质

• 沸点：
  450.4±40.0 °C(Predicted)
• 密度：
  0.954±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  47.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-N,N-bis[2'-(tert-butyldimethylsilyloxy)ethyl]aniline 在 4-二甲氨基吡啶 、 dibutyl laurate 、 triethylamine trihydrofluoride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 di-tert-butyl 4-{[2'-(N,N-bis(2''-mesyloxyethyl)amino)phenyl]carbamoyloxymethyl}phenyloxycarbonyl-L-glutamate
  参考文献：
  名称：

  Self-Immolative Nitrogen Mustards Prodrugs Cleavable by Carboxypeptidase G2 (CPG2) Showing Large Cytotoxicity Differentials in GDEPT

  摘要：

  Nineteen novel potential self-immolative prodrugs and their corresponding drugs have been synthesized for gene-directed enzyme prodrug therapy (GDEPT) with carboxypeptidase G2 (CPG2) as the activating enzyme. The compounds are derived from o- and p-amino and p-methylamino aniline nitrogen mustards. Their aqueous stability, kinetics of drug release by CPG2, and cytotoxicity in the colon carcinoma cell line WiDr, expressing either surface-tethered CPG2 (stCPG2(Q)3) or control beta-galactosidase, are assessed. The effect of various structural features on stability, kinetics of activation, and biological activity is discussed. The p-methylamino prodrugs are the most stable compounds from this series, with the largest cytotoxicity differentials between CPG2-expressing and nonexpressing cells. The most potent compounds in all series are prodrugs of bis-iodo nitrogen mustards. 4-{N-[4'-Bis(2"-iodoethyl)aminophenyll-N'-methylcarbamoyloxymethyl}phenylcarbamoyl-L-glutamic acid, compound 39b, is 124-fold more cytotoxic to WiDr cells expressing CPG2 than to cells expressing beta-galactosidase. An additional six compounds show better cytotoxicity differential than the published N-{4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl}-L-glutamic acid (CMDA) prodrug.

  DOI：

  10.1021/jm020462i
• 作为产物：
  描述：

  N,N-bis(2-hydroxyethyl)-2-nitroaniline 在 palladium on activated charcoal 咪唑 、 氢气 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-amino-N,N-bis[2'-(tert-butyldimethylsilyloxy)ethyl]aniline
  参考文献：
  名称：

  Self-Immolative Nitrogen Mustards Prodrugs Cleavable by Carboxypeptidase G2 (CPG2) Showing Large Cytotoxicity Differentials in GDEPT

  摘要：

  Nineteen novel potential self-immolative prodrugs and their corresponding drugs have been synthesized for gene-directed enzyme prodrug therapy (GDEPT) with carboxypeptidase G2 (CPG2) as the activating enzyme. The compounds are derived from o- and p-amino and p-methylamino aniline nitrogen mustards. Their aqueous stability, kinetics of drug release by CPG2, and cytotoxicity in the colon carcinoma cell line WiDr, expressing either surface-tethered CPG2 (stCPG2(Q)3) or control beta-galactosidase, are assessed. The effect of various structural features on stability, kinetics of activation, and biological activity is discussed. The p-methylamino prodrugs are the most stable compounds from this series, with the largest cytotoxicity differentials between CPG2-expressing and nonexpressing cells. The most potent compounds in all series are prodrugs of bis-iodo nitrogen mustards. 4-{N-[4'-Bis(2"-iodoethyl)aminophenyll-N'-methylcarbamoyloxymethyl}phenylcarbamoyl-L-glutamic acid, compound 39b, is 124-fold more cytotoxic to WiDr cells expressing CPG2 than to cells expressing beta-galactosidase. An additional six compounds show better cytotoxicity differential than the published N-{4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl}-L-glutamic acid (CMDA) prodrug.

  DOI：

  10.1021/jm020462i

文献信息

• Self-Immolative Nitrogen Mustards Prodrugs Cleavable by Carboxypeptidase G2 (CPG2) Showing Large Cytotoxicity Differentials in GDEPT
  作者：Dan Niculescu-Duvaz、Ion Niculescu-Duvaz、Frank Friedlos、Jan Martin、Panos Lehouritis、Richard Marais、Caroline J. Springer

  DOI：10.1021/jm020462i

  日期：2003.4.1

  Nineteen novel potential self-immolative prodrugs and their corresponding drugs have been synthesized for gene-directed enzyme prodrug therapy (GDEPT) with carboxypeptidase G2 (CPG2) as the activating enzyme. The compounds are derived from o- and p-amino and p-methylamino aniline nitrogen mustards. Their aqueous stability, kinetics of drug release by CPG2, and cytotoxicity in the colon carcinoma cell line WiDr, expressing either surface-tethered CPG2 (stCPG2(Q)3) or control beta-galactosidase, are assessed. The effect of various structural features on stability, kinetics of activation, and biological activity is discussed. The p-methylamino prodrugs are the most stable compounds from this series, with the largest cytotoxicity differentials between CPG2-expressing and nonexpressing cells. The most potent compounds in all series are prodrugs of bis-iodo nitrogen mustards. 4-N-[4'-Bis(2"-iodoethyl)aminophenyll-N'-methylcarbamoyloxymethyl}phenylcarbamoyl-L-glutamic acid, compound 39b, is 124-fold more cytotoxic to WiDr cells expressing CPG2 than to cells expressing beta-galactosidase. An additional six compounds show better cytotoxicity differential than the published N-4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl}-L-glutamic acid (CMDA) prodrug.